Focal adhesion kinase (FAK) is a 125 kDa non-receptor protein tyrosine kinase that is concentrated at focal adhesions, the contact sites between cells and the extracellular matrix (ECM). FAK is involved in integrin signaling, cellular motility, and survival and is expressed at high levels in breast, colon, thyroid cancers, and in sarcomas. Interruption of normal FAK function causes cancer cells to become non-adherent and to undergo apoptosis.
Despite progress in understanding the biology of FAK and its signaling complex, much remains unknown as to how FAK interacts with its signaling partners to resist activation of the apoptotic cascade. The carboxy-terminus of FAK contains the focal adhesion targeting (FAT) domain of the protein. The FAT domain is critical for recruitment of FAK to focal adhesions and contains binding sites for two focal adhesion-associated proteins, paxillin and talin. Agents that modulate binding of FAK or FAT to other cellular components would be of use in further understanding the role of FAK in apoptosis, and may also be useful for killing cancer cells.